eMedicine Specialties > Pediatrics: General Medicine > Hematology

Anemia, Fanconi: Follow-up

Author: Blanche P Alter, MD, MPH, FAAP, Adjunct Faculty, Medical Genetics Fellowship Program, National Human Genome Research Institute; Adjunct Professor of Pediatrics, George Washington University School of Medicine and Health Scieces; Visiting Professor of Pediatrics, Johns Hopkins School of Medicine; Senior Clinician, Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute
Coauthor(s): Jeffrey M Lipton, MD, PhD, Professor, Elmezzi Graduate School of Molecular Medicine, Director, Patient Oriented Research, Feinstein Institute for Medical Research; Director, Pediatric Hematology/Oncology and Stem Cell Transplantation, Schneider Children's Hospital; Director of Hematology-Oncology and Stem Cell Transplantation, Children's Health Network, North Shore/Long Island Jewish Health System
Contributor Information and Disclosures

Updated: Sep 9, 2009

Follow-up

Further Inpatient Care

  • Inpatient care of Fanconi anemia (FA) may be needed for complications of bone marrow failure (eg, bleeding, infection).
  • Transfusions may be given as inpatient or outpatient treatment.
  • Hematopoietic stem cell transplantation is currently an inpatient procedure.
  • Hospitalization may be needed for treatment of other complications (eg, leukemia, tumors).

Further Outpatient Care

  • Blood counts are recommended at 3-month intervals or more often as needed. Transfusions of red cells or platelets can be given to outpatients. Annual or more frequent bone marrow examinations can be outpatient procedures.

Deterrence/Prevention

  • Carrier screening can be offered as part of reproductive counseling for groups in which a founder effect and a carrier rate of more than 1 per 100 population are recognized. In utero prenatal diagnosis is available, and preimplantation genetic diagnosis may be possible.
  • In families in which the mutation has been identified in a proband or through carrier screening, in vitro fertilization and preimplantation genetic diagnosis may be offered.
  • In families with an affected proband, cord blood may be saved for future use as a source of hematopoietic stem cells at the birth of a sibling. In vitro fertilization and preimplantation genetic diagnosis can be used to identify a fetus that is an human leukocyte adhesion (HLA)-match and does not have Fanconi anemia.

Complications

  • Possible complications include hemorrhages, infections, leukemia, myelodysplastic syndrome, liver tumors, and other cancers.
  • Leukemia was reported in more than 150 patients with Fanconi anemia (out of more than 1800 reported in the literature), of which 95% were acute myeloid leukemias (usually rare in children).
  • Myelodysplastic syndrome was reported in more than 100 patients; many of these patients did not develop leukemia but died from complications of impaired marrow function.
  • Liver tumors occurred in more than 40 patients, often in the context of aplastic anemia or other tumors, and were not usually malignant (although two thirds were histologically hepatomas and the rest were adenomas).
  • More than 175 solid tumors were reported in more than 160 patients. In order of frequency, these tumors were tumors of the oropharynx, esophagus, vulva, brain, skin (nonmelanoma), cervix, breast, kidney, lung, lymph nodes (lymphoma), stomach, and colon, followed by osteogenic sarcoma and retinoblastoma. At least 18 oral cancers have been reported in patients with Fanconi anemia following bone marrow transplantation.
  • Patients with Fanconi anemia in the D1/BRCA2 and N/PALB2 groups have inordinately high rates of acute myeloid leukemias, brain tumors, and Wilms tumors, with a cumulative incidence of at least one of these cancers of 95% by age 5 years.

Prognosis

  • Treatment of aplastic anemia with medications, supportive use of blood products, and stem cell transplantation increases the life expectancy beyond the projected median of approximately age 30 years.
  • Cancer prevention and screening to identify early malignancies may reduce the mortality rate from cancer.
  • Although many patients with Fanconi anemia are short and have skeletal anomalies, intelligence is usually normal, and education and career planning should be encouraged.

Patient Education

  • Educate patients and their families regarding behaviors with risk of bleeding as well as maintenance of hygiene to reduce infections. Emphasize the need to comply with medications and transfusions. Educate patients and their families about cancer prevention (eg, smoking, drinking, diet, lifestyle) and cancer screening (eg, bone marrow, oropharyngeal, and gynecological examinations).
  • The genetic basis of Fanconi anemia needs to be explained, and apparently unaffected siblings should be tested for Fanconi anemia homozygosity. Provide genetic counseling to parents, caregivers, and other carriers or potential carriers with regard to the risk of recurrence. Discuss phenotypic variability within a family.
  • For excellent patient education resources, visit eMedicine's Blood and Lymphatic System Center. Also, see eMedicine's patient education article Anemia.

Miscellaneous

Medicolegal Pitfalls

  • Failure to diagnose aplastic anemia or leukemia may lead to delays in treatment. The diagnosis of Fanconi anemia (FA) must be made to avoid the inappropriate use of immunosuppressive therapy for aplastic anemia, the use of toxic levels of chemotherapy or radiotherapy in leukemia or solid tumors, or toxic types of preparation for stem cell transplantation. Fanconi anemia is one of the few forms of aplastic anemia in which the response to androgens is more than 50%.
  • Related transplant donors must be proven not to have Fanconi anemia in order for a transplantation to succeed.
  • Patients who have tumors that are characteristic of Fanconi anemia but who present without the usual risk factors for those tumors need to be screened for Fanconi anemia (eg, head and neck cancer in a 20-year-old woman who does not smoke or drink).
  • Mild forms of Fanconi anemia may be missed, placing future pregnancies in that family at risk for Fanconi anemia. Possible probands with characteristic birth defects, undiagnosed cytopenias, or macrocytosis should be evaluated for Fanconi anemia.

Special Concerns

  • The diagnosis of FA is not made using routine laboratory tests, but it must be considered and tested for using chromosome breakage in blood or fibroblasts, or germline mutation analysis. Siblings who do not apparently have FA need to be screened for occult FA.
 


More on Anemia, Fanconi

Overview: Anemia, Fanconi
Differential Diagnoses & Workup: Anemia, Fanconi
Treatment & Medication: Anemia, Fanconi
Follow-up: Anemia, Fanconi
Multimedia: Anemia, Fanconi
References
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References

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  2. Callen E, Casado JA, Tischkowitz MD, et al. A common founder mutation in FANCA underlies the world's highest prevalence of Fanconi anemia in Gypsy families from Spain. Blood. Mar 1 2005;105(5):1946-9. [Medline].

  3. Rosenberg PS, Greene MH, Alter BP. Cancer incidence in persons with Fanconi anemia. Blood. Feb 1 2003;101(3):822-6. [Medline].

  4. Rosenberg PS, Alter BP, Ebell W. Cancer risks in Fanconi anemia: findings from the German Fanconi Anemia Registry. Haematologica. Apr 2008;93(4):511-7. [Medline].

  5. Verlander PC, Kaporis A, Liu Q, et al. Carrier frequency of the IVS4 + 4 A-->T mutation of the Fanconi anemia gene FAC in the Ashkenazi Jewish population. Blood. Dec 1 1995;86(11):4034-8. [Medline].

  6. Dalle JH. HSCT for Fanconi anemia in children: factors that influence early and late results. Bone Marrow Transplant. Oct 2008;42 Suppl 2:S51-3. [Medline].

  7. Pasquini R, Carreras J, Pasquini MC, Camitta BM, Fasth AL, Hale GA. HLA-matched sibling hematopoietic stem cell transplantation for fanconi anemia: comparison of irradiation and nonirradiation containing conditioning regimens. Biol Blood Marrow Transplant. Oct 2008;14(10):1141-7. [Medline].

  8. Alter BP. Cancer in Fanconi anemia, 1927-2001. Cancer. Jan 15 2003;97(2):425-40. [Medline].

  9. Alter BP. Inherited bone marrow failure syndromes. In: Nathan DG, Orkin SH, Ginsburg D, Look T, eds. Hematology of Infancy and Childhood. 6th ed. Philadelphia, Pa: Harcourt Health Sciences; 2003:280-365.

  10. Alter BP, Caruso JP, Drachtman RA, et al. Fanconi anemia: myelodysplasia as a predictor of outcome. Cancer Genet Cytogenet. Mar 2000;117(2):125-31. [Medline].

  11. Alter BP, Rosenberg PS, Brody LC. Clinical and molecular features associated with biallelic mutations in FANCD1/BRCA2. J Med Genet. Jan 2007;44(1):1-9. [Medline].

  12. Bagby GC, Alter BP. Fanconi anemia. Semin Hematol. Jul 2006;43(3):147-56. [Medline].

  13. Faivre L, Guardiola P, Lewis C, et al. Association of complementation group and mutation type with clinical outcome in fanconi anemia. European Fanconi Anemia Research Group. Blood. Dec 15 2000;96(13):4064-70. [Medline].

  14. Garcia-Higuera I, Taniguchi T, Ganesan S, et al. Interaction of the Fanconi anemia proteins and BRCA1 in a common pathway. Mol Cell. Feb 2001;7(2):249-62. [Medline].

  15. Joenje H, Patel KJ. The emerging genetic and molecular basis of Fanconi anaemia. Nat Rev Genet. Jun 2001;2(6):446-57. [Medline].

  16. Kupfer GM, Green AM. Fanconi anemia. In: Bagby GC, Meyers G. Hematology/Oncology Clinics of North America. Vol 23. 2nd ed. Philadelphia, PA: WB Saunders Company; 2009:193-214.

  17. [Guideline] Langlois S, Wilson RD. Carrier screening for genetic disorders in individuals of Ashkenazi Jewish descent. J Obstet Gynaecol Can. Apr 2006;28(4):324-43. [Medline].

  18. Rosenberg PS, Huang Y, Alter BP. Individualized risks of first adverse events in patients with Fanconi anemia. Blood. Jul 15 2004;104(2):350-5. [Medline].

  19. Rosenberg PS, Socie G, Alter BP, Gluckman E. Risk of head and neck squamous cell cancer and death in patients with Fanconi anemia who did and did not receive transplants. Blood. Jan 1 2005;105(1):67-73. [Medline].

  20. Rosenberg PS, Socie G, Alter BP, Gluckman E. Risk of head and neck squamous cell cancer and death in patients with Fanconi anemia who did and did not receive transplants. Blood. Jan 1 2005;105(1):67-73. [Medline].

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  23. Young NS, Alter BP. Aplastic Anemia: Acquired and Inherited. Philadelphia, PA: WB Saunders Co; 1994:410.

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Further Reading

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Keywords

Fanconi anemia, FA, constitutional aplastic anemia, bone marrow failure, inherited bone marrow failure syndrome, aplastic anemia, leukemia, myelodysplastic syndrome, liver adenoma, hepatoma, radial ray anomalies, poor growth, genitourinary problems, short stature, skin pigmentation, café au lait spots, petechiae, bruises, bruising, pallor, fatigue, infections, thumb anomalies, thumb and radial anomalies, abnormal male gonads, microcephaly, eye anomalies, structural renal defects, low birth weight, developmental delay, abnormal ears, abnormal hearing, Estren Dameshek Fanconi anemia, pancytopenia, treatment, diagnosis

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Contributor Information and Disclosures

Author

Blanche P Alter, MD, MPH, FAAP, Adjunct Faculty, Medical Genetics Fellowship Program, National Human Genome Research Institute; Adjunct Professor of Pediatrics, George Washington University School of Medicine and Health Scieces; Visiting Professor of Pediatrics, Johns Hopkins School of Medicine; Senior Clinician, Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute
Blanche P Alter, MD, MPH, FAAP is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Association for the Advancement of Science, American Federation for Medical Research, American Pediatric Society, American Society for Clinical Investigation, American Society of Hematology, International Society of Hematology, New York Academy of Sciences, Phi Beta Kappa, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Coauthor(s)

Jeffrey M Lipton, MD, PhD, Professor, Elmezzi Graduate School of Molecular Medicine, Director, Patient Oriented Research, Feinstein Institute for Medical Research; Director, Pediatric Hematology/Oncology and Stem Cell Transplantation, Schneider Children's Hospital; Director of Hematology-Oncology and Stem Cell Transplantation, Children's Health Network, North Shore/Long Island Jewish Health System
Jeffrey M Lipton, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Children's Oncology Group, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Medical Editor

J Martin Johnston, MD, Associate Professor of Pediatrics, Mercer University School of Medicine; Director of Pediatric Hematology/Oncology, Backus Children's Hospital; Consulting Oncologist/Hematologist, St Damien's Pediatric Hospital
J Martin Johnston, MD is a member of the following medical societies: American Society of Pediatric Hematology/Oncology
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Steven K Bergstrom, MD, Assistant to the Chairman, Department of Pediatrics, Division of Hematology-Oncology, Kaiser Permanente Medical Center of Oakland
Steven K Bergstrom, MD is a member of the following medical societies: Alpha Omega Alpha, American Society of Clinical Oncology, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Children's Oncology Group, and International Society for Experimental Hematology
Disclosure: Nothing to disclose.

CME Editor

Samuel Gross, MD, Professor Emeritus, Department of Pediatrics, University of Florida; Clinical Professor, Department of Pediatrics, University of North Carolina; Adjunct Professor, Department of Pediatrics, Duke University
Samuel Gross, MD is a member of the following medical societies: American Association for Cancer Research, American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology, American Society of Hematology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Chief Editor

Max J Coppes, MD, PhD, MBA, Senior Vice President, Children's National Medical Center (Center for Cancer and Blood Disorders); Director, Center for Cancer and Immunology Research, Children's Research Institute, Children's National Medical Center; Professor of Medicine, Oncology, and Pediatrics, Georgetown University
Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American Association for Cancer Research, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

 
 
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